This invention relates to a novel protein designated Rib (and subfragments, variants and multiples thereof) which confers immunity to most invasive straw of the group B Streptococcus, a procedure for purification of the protein, antibodies specific to the protein, a reagent kit and a pharmaceutical composition comprising the protein or fragments thereof.
During the last three decades, the group B Streptococcus has emerged as a major cause of neonatal disease in the Western world. In the United States alone, there are about 10,000 cases per year of invasive disease caused by this bacterium. These infections have an overall mortality of about 20%, and many of the infants that survive have permanent neurological sequelae. In view of these findings, a large effort has been made to find methods of prevention and treatment and to analyze the mechanisms by which group B streptococci cause infections.
About 20% of all women are vaginal carriers of the group B Streptococcus, and vertical transmission from the maternal genital tract is probably the most common source of infection in neonatal disease caused by this bacterium. However, only 1 to 2% of the infants that are colonized by the group B Streptococcus at birth are afflicted by serious infection. Other factors than exposure to the bacterium during birth must therefore contribute to the development of neonatal disease. Mothers of infected infants have significantly lower levels of antibodies to the type III capsule, which implies that these antibodies are important for protection against neonatal disease (Baker, C. J. and D. L. Kasper, N. Engl. J. Med. 1976, 294:753).
Group B streptococcal strains are divided into four major serotypes (Ia, Ib, II, and III) based on the structure of the polysaccharide capsule (Baker, J Inf Dis 1990. 161: 917). Serotypes I, II, and III occur in roughly equal proportions among strains in the normal flora, but type III accounts for about two-thirds of all isolates from invasive infections. Since the capsule is a known virulence factor, it has been studied in considerable detail, in particular in type III strains. Efforts have been made to develop a vaccine, in which the type III polysaccharide capsule would be an essential component. However, use of the polysaccharide capsule as a vaccine may give problems due to crossreactions with human tissues (Pritchard et al., Infect Immun 1992. 60: 1598). It would therefore be very valuable if one could develop a vaccine based on proteins rather than on polysaccharides.
The group B Streptococcus can also cause mastitis in cows, a bovine disease that is of considerable economical importance. Development of a vaccine against group B streptococcal infections is therefore of interest also in veterinary medicine.
Two group B streptococcal cell surface proteins have previously been studied in detail: the alpha and beta proteins. These proteins confer protective immunity to strains expressing the proteins, but they are of limited interest for group B streptococcal disease, since they are usually not expressed by type III strains, which cause the majority of serious infections.